Corticoid-Verdünnungen

  • K. H. Müller

Zusammenfassung

Die rezepturmäßige Verdünnung stark wirkender Corticoid-Dermatica des Handels ist zu einem von Ärzten, Apothekern und Arzneifabrikanten heftig umstrittenen Thema geworden. Es wird der Versuch einer Sichtung der Publikationen unternommen, die sich mit dem Thema beschäftigen und die Pro und Contra dieser Praxis zur Diskussion stellen. So werden nach einer Begründung der Rezeptur von Verdünnungen deren galenische, biopharmazeutische, chemische und mikrobiologische Aspekte besprochen. Schließlich wird auf Alternativlösungen hingewiesen, die der Erhöhung der Therapiesicherheit dienen.

Summary

Prescription of potent topical corticoid preparations diluted with various vehicles has become an issue of disputation among physicians, pharmacists, and pharmaceutical firms. The recent literature on this problem is reviewed and discussed with particular respect of the reasons of “pro” and “contra” of this prescriptive practice in medicine. Various risky aspects of dilutory formulation with regard to pharmaceutics, biopharmaceutics, chemistry, and microbiology are pointed out. Some alternative proposals to improve the safety of therapy is presented.

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Literatur

  1. Altmeyer, P.: Über die Wirksamkeit von Steroidsalben unterschiedlicher Konzentration. Eine experimentelle Studie. Ärztl. Kosmetol. 10, 311 (1980).Google Scholar
  2. Asche, H, Gay, M u.a.: Einfluß des Behälters auf die Anfälligkeit von Dermatika-Grundlagen gegenüber mikrobieller Kontamination. Pharm. Industrie 40, 1212 (1978).Google Scholar
  3. Baird, R M, Brown, W R L, Shooter, R A.: Pseudomonas aeruginosa in hospital pharmacies. Brit. med. J. 1, 511 (1976).PubMedCrossRefGoogle Scholar
  4. Borovian, G E.: Pseudomonas cepacia: growth in and adaptability to increased preservative concentrations. J. Soc. Cosmet. Chem. 34, 197 (1983).Google Scholar
  5. Brookes, FL, Hugo, W B, Denyer, S P.: Transformation of betamethason 17-valerate by skin microflora. J. Pharm. Pharmacol. (Lond.) 33, 74 P (1981).Google Scholar
  6. Bundgaard, H.: The possible implication of steroid-glyoxal degradation products in allergic reactions to corticosteroids. Arch. Pharm. Chem., Sci. Ed. (Kbh.) 8, 83 (1980).Google Scholar
  7. Bundgaard, H, Hansen, J.: Studies on the stability of corticosteroids. IV. Formation and degradation kinetics of 21-dehydrocorticosteroids, key intermediates in the oxidative decomposition of 21- hydroxy corticosteroids. Arch. Pharm. Chem., Sci. Ed. (Kbh.) 8, 187 (1980).Google Scholar
  8. Bundgaard, H, Hansen, J.: Studies on the stability of corticosteroids. VI. Kinetics of the rearrangement of betamethasone-17-valerate to the 21-va- lerate ester in aqueous solution. Intern. J. Pharmaceut. (Amsterdam) 7, 197 (1981).Google Scholar
  9. Burdick, K H, Poulsen, B, Place, V A.: Extemporaneous formulation of corticosteroids for topical usage. JAMA 211, 462 (1970).PubMedCrossRefGoogle Scholar
  10. Busse, M J.: Dangers of dilution of topical steroids. Pharm. J. (Lond.) 220, 25 (1978).Google Scholar
  11. Busse, M J, Hunt, P u.a.: Release of betamethasone derivatives from ointments — in vivo and in vitro studies. Brit. J. Derm. 81, Suppl. 4, 103 (1969).CrossRefGoogle Scholar
  12. Champion, R N, Goldin, D.: Clinical aspects of topical therapy. Pharm. J. (Lond.) 218, 328 (1975).Google Scholar
  13. Clement, M, Hehir, M u.a.: The effect of epidermal DNA synthesis of a combination of topical steroid with either dithranol or tar as used for psoriasis. Brit. J. Derm. 109, 327 (1983).PubMedCrossRefGoogle Scholar
  14. Das Gupta V: Stability of triamcinolone acetonide solutions as determined by high-performance chromatography, J. Pharm. Sci. 72, 1453 (1983).PubMedCrossRefGoogle Scholar
  15. Dolder, R.: Inkompatibilitäten bei der Therapie mit dermatologischen Externa. Aktuelle. Derm. 6, 213 (1980).Google Scholar
  16. Feather, J W, Ryatt, K S u.a.: Reflectance spectrophotometric quantification of skin colour changes induced by topical corticosteroid preparations. Brit. J. Derm. 106, 437 (1982).PubMedCrossRefGoogle Scholar
  17. Feuerstein, W.: Die Tätigkeit niedergelassener Dermatologen anhand einer Umfrage. Schrifttum u. Praxis 12, 54 (1981).Google Scholar
  18. Fröhlich, H H.: Externa zur Pflege und Behandlung der Haut; in Schneider, W., Fröhlich, H H.: Die Haut. Teil A. Pflege und Behandlung. Bayerische Landesapothekenkammer, München, 1979, p.42.Google Scholar
  19. Früh, H.: Einfluß von Urea in einem Kortikoid-Dermatikum auf die Vasokonstriktion. Z. Hautkr. 58, 1203 (1983).PubMedGoogle Scholar
  20. Gardi, R, Vitali, R, Ercoli, A.: Derivati di condensazione nella catena laterale di corticosteroidi. Nota III. Preparazione e reazioni di 17-monoesteri. Gazz. chim. ital. 93, 431 (1963).Google Scholar
  21. Gardi, R.: New reactions in corticosteroid side chain; in Martini, L, Pecile, A.: Hormonal steroids. Academic Press, New York, London, 1965, p. 99.Google Scholar
  22. Gartmann, H.: Corticosteroide in der Behandlung von Dermatosen. Med. Mschr. Pharmazeut. 2, 45 (1979).Google Scholar
  23. Gibson, J R, Darley, C u.a.: The dilution of proprietary corticosteroid ointments - an attempt to evaluate relative clinical potencies. Brit. J. Derm. 106, 445 (1982).PubMedCrossRefGoogle Scholar
  24. Gibson, J R, Kirsch, J u.a.: An attempt to evaluate the relative potencies of various diluted and undiluted proprietary corticosteroid preparations. Brit. J. Derm. 109, Suppl. 25, 114 (1983).PubMedGoogle Scholar
  25. Hadgraft, J W.: The changing pattern of topical dermatological therapy. J. Soc. Cosmet. Chem. 20, 663 (1969).Google Scholar
  26. Hadgraft, J W.: Recent progress in the formulation of vehicles for topical application. Brit. J. Derm. 87, 386 (1972).PubMedCrossRefGoogle Scholar
  27. Hallam, N F.: The use and abuse of topical corticosteroids in dermatology. Scott, med. J. 25, 287 (1980).Google Scholar
  28. Hansen, J, Bundgaard, H.: Studies on the stability of corticosteroids. I. Kinetics of degradation of hydrocortisone in aqueous solution. Arch. Pharm. Chem., Sci. Ed. (Kbh.) 7, 135 (1979).Google Scholar
  29. Hidaka, T u.a.: Studies on betamethasone: Behaviour of betamethasone in acid or alkaline medium, photolysis and oxidation. Yakugaku Zasshi. 100, 72 (1980).PubMedGoogle Scholar
  30. Hoffmann, R-R.: Corticoidpräparate in der Hauttherapie; in Morck, H, Liekefeldt, H, Schneider, L.: Offizinpharmazie. Bd. 2. Gg. Thieme Verlag, Stuttgart, 1980, p. 42.Google Scholar
  31. Huber, H P, Pflugshaupt, Ch.: Ergebnisse einer systematischen Kortikoid-Grundlagen-Intervalltherapie. Schweiz. Rdsch. Med. (Praxis) 68, 821 (1979).Google Scholar
  32. Kessler, H-J.: Local antiseptics versus antibiotics in topical therapy - the emergence of microbial resistance. Mykosen 23, 285 (1980).PubMedGoogle Scholar
  33. Kidd, K: Percutaneous absorption, vehicles and dermatological prescribing. Aust. J. Derm. 16, 60 (1975).CrossRefGoogle Scholar
  34. Kirsch, J M, Gibson, J R, Darley, C R.: The stability and blanching efficiency of betamethasone-17-valerate in emulsifying ointment. Brit. J. Derm. 108, 250 (1983).PubMedCrossRefGoogle Scholar
  35. Li Wan Po, A, Irwin, W J, Yip, Y W. (I): High-performance liquid chromatographic assay of betamethasone-17-valerate and its degradation products. J. Chromatogr. (Amst.) 176, 399 (1979).Google Scholar
  36. Li Wan Po, A, Irwin, W J, Yip, Y W (II): Stability of topical steroids. Proc. Analyt. Div. Chem. Soc. 1979, 333.Google Scholar
  37. Li Wan Po, A, Irwin, W J.: High-performance liquid chromatography - techniques and applications. J. Clin. Hosp. Pharmacy (Lond.) 5, 107 (1980).Google Scholar
  38. Magnus, A D, Haigh, J M, Kanfer, I.: Release of betamethasone 17-valerate from extemperaneous dilutions of a proprietaiy topical cream. Dermatologica (Basel) 163, 331 (1981).CrossRefGoogle Scholar
  39. Main, R A, White, M I.: Choice of topical corticosteroids. Practitioner 219, 456 (1977).PubMedGoogle Scholar
  40. McKenzie, A W, Atkinson, R M.: Topical activities of betamethasone esters in man. Arch. Derm. (Chicago) 89, 741 (1964).CrossRefGoogle Scholar
  41. Mehta, A C, Calvert, R T, Ryatt, K S.: Betamethasone 17-valerate — An investigation into its stability in Betnovate after dilution with Emulsifying Ointment: quantitation of degradation products. Brit. J. Pharm. Pract. 4, 10 (1982).Google Scholar
  42. Miller, J A, Munro, D D.: Topical corticosteroids: clinical pharmacology and therapeutic use. Drugs 19, 119 (1980).PubMedCrossRefGoogle Scholar
  43. Mooney, A F.: Dilution of topical corticosteroid formulations. Brit. J. Derm. 90, 109 (1974).PubMedCrossRefGoogle Scholar
  44. Noble, W C, Savin, JA.: Steroid cream contaminated with Pseudomonas aeruginosa. Lancet 1966, I, 347.CrossRefGoogle Scholar
  45. Nowak, G A.: Mikrobiologische Anforderungen bei kosmetischen Mitteln. Parfüm, u. Kosmet. 60, 8 (1979); Die Konservierung kosmetischer und pharmazeutischer Produkte unter Berücksichtigung der GMP. ibid. 60, 130 (1979).Google Scholar
  46. Orr, NA, Hill, E A, Smith, J F.: Distribution of powdered drugs in ointment bases. Int. J. Pharm. Techn. Prod. Mfr. 1, 4 (1980).Google Scholar
  47. >Paetzold, O-H.: Zur Frage der Infektiosität mikrobiell verunreinigter Externa — Eine spezielle Studie —. Ärztl. Kosmetol. 11, 225 (1981).Google Scholar
  48. Pflugshaupt, Ch.: Diskontinuierliche topische Corticoidtherapie, Zbl. Haut- u. Geschl.-Kr. 148, 1229 (1983).Google Scholar
  49. Pierard, G-E.: La tachyphylaxie et les corticost6roides topiques. Nouv. Derm. 2, 8 (1983).Google Scholar
  50. Rauch, H J.: Anmerkungen zur Kurzzeitbehandlung der Psoriasis vulgaris mit Anthralin. Aktuelle Derm. 9, 120 (1983).Google Scholar
  51. Reynolds, E F, Prasad, A B.: Martindale - The Extra Pharmacopoeia, 28. Ed., The Pharmaceutical Press, London, 1982, p. 462.Google Scholar
  52. Ryatt, K S, Feather, J W u.a.: The stability and blanching efficacy of betamethasone-17-valerate in Emulsifying Ointment. Brit. J. Derm. 107, 71 (1982); 108, 251 (1983).PubMedCrossRefGoogle Scholar
  53. Savin, JA. (I): Pseudomonas aeruginosa infections in a skin ward. Trans. Rep. St. John’s Hosp. derm. Soc. (Lond.) 1967, 75.Google Scholar
  54. Savin, JA. (II): The microbiology of topical preparations in pharmaceutical praxis. 1. Clinical aspects. Pharmaceut. J. (Lond.) 1967, 285.Google Scholar
  55. Savin, J A.: Topical steroids and bacterial infection. Brit. J. Derm. 94, Suppl. 12, 125 (1976).PubMedCrossRefGoogle Scholar
  56. Schalla, W.: Euromed-Gespräch: Kortison? - Warum nicht! Euromed 23, 476 (1983).Google Scholar
  57. Smith, J F.: The incidence of topical steroid dilutions. J. Clin. Hosp. Pharmacy (Lond.) 7, 137 (1982).Google Scholar
  58. Smith, J F, Beveridge, E G, Orr, NA.: Dilution of betamethasone ointment. Brit. J. Derm. 108, 248 (1983).PubMedCrossRefGoogle Scholar
  59. Sneddon, I B.: Clinical use of topical corticosteroids. Drugs 11, 193 (1976).PubMedCrossRefGoogle Scholar
  60. Stoughton, R B.: Vasoconstrictor activity and percutaneous absorption of glucocorticosteroids: A direct comparison. Arch. Derm. (Chicago) 99, 753 (1969).CrossRefGoogle Scholar
  61. Stoughton, R B.: Topical corticoid therapy: A round table discussion, Part V. Cutis (N. Y.) 25, 441 (1980).Google Scholar
  62. The Pharmaceutical Codex, 11. Ed., The Pharmaceutical Press, London, 1979, p. 98, 99.Google Scholar
  63. The degradation of triamcinolone acetonide in aqueous solution: influence of the cyclic ketal function.Google Scholar
  64. Timmins P. u. Gray E A.: J. Pharmacol. 35, 175 (1983). - Transparenz-telegramm, A.T.I. Arzneimittelinformation Berlin GmbH, Berlin, 1983, p. 878.CrossRefGoogle Scholar
  65. Vitali, R, Gardi, R.: Hydrolysis of corticosteroid 17,21-alkylorthoesters in buffered medium. Farmaco, Ed. Sci. (Pavia) 27, 878 (1973).Google Scholar
  66. Wallhäußer, K H.: Die mikrobielle Reinheit von Arzneimitteln in der Hand des Verbrauchers. Dtsch. Apoth. Ztg. 118, 1510 (1978).Google Scholar
  67. Weirich, E G.: Zur Pharmakologie der Dermocorticoide. Z. Hautkr. 53, 189, 247 (1977).Google Scholar
  68. Weitgasser, H.: Erfahrungen mit magistraliter zubereiteten Verdünnungen eines neuen Flumethasonpivalat-Triclosan-Dermatikums in der dermatologischen Praxis. Ergebnisse einer multizentrischen Prüfung. Wien. med. Wschr. 1979, 193.Google Scholar
  69. Wendt, H, Frosch, P J.: Clinico-pharmacological models for the Assay of topical corticoids. Karger, Basel, 1982, p. 13.Google Scholar
  70. Whitefield, M.: Topical steroids. Lancet 1977, 925.Google Scholar
  71. Woodbridge, P A, Sparkes, C G.: Managing chronic skin conditions with two differing topical corticosteroids. Dermatologi- ca (Basel) 158, 299 (1979).CrossRefGoogle Scholar
  72. Woodford, R.: Investigation of the release characteristics of Unguentum Merck as a diluent for topical corticosteroid preparations. Curr. Ther. Res. Clin. Exp. 29, 17 (1981).Google Scholar
  73. Yip, Y W, Li Wan Po, A.: The stability of betamethasone-17-valerate in semi-solid bases. J. Pharm. Pharmacol. (Lond.) 31, 400 (1979).Google Scholar
  74. Yip, Y W, Li Wan Po, A, Irwin, W J.: Kinetics of decomposition and formulation of hydrocortisone butyrate in semiaqueous and gel systems. J. pharm. Sci. 72, 776 (1983).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • K. H. Müller
    • 1
  1. 1.Dr. Spirig AG, Pharmazeutische PräparateOltenSchweiz

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